Perinatal exposure to dioxins and dioxin-like compounds and infant growth and body mass index at seven years: A pooled analysis of three European birth cohorts
Introduction
Dioxins and dioxin-like compounds (DLCs) are among the most toxic pollutants known to science. This class of compounds includes dioxins or polychlorinated dibenzo-p-dioxins (PCDDs), of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic, polychlorinated dibenzofurans (PCDFs), as well as some polychlorinated biphenyls (PCBs) [hereafter “dioxins” refers to dioxins and DLCs]. Dioxins are largely unintentional by-products of various industrial processes, such as smelting and herbicide and pesticide manufacture. Although stricter legislation has curtailed environmental release of these pollutants, they are prevalent in the environment and likely to remain so for some time due to biomagnification, bioaccumulation and long half-lives. TCDD has a half-life of 7–8 years in humans (Kogevinas, 2001), while some other DLCs have half-lives of more than a decade (Milbrath et al., 2009). > 90% of human exposure is through food (Djien Liem et al., 2000). Infants are then exposed to maternal blood concentrations in utero and through breast milk and food during infancy. During a short period of breastfeeding, they are exposed to concentrations that are 10–20 fold higher than the recommended exposure concentrations (Stigum et al., 2005).The biological mechanism of action of all these compounds is mediated via activation of the cellular protein aryl hydrocarbon receptor (AhR) (Birnbaum, 1994). The World Health Organisation has developed toxic equivalency factors (TEF) for DLCs relative to TCDD based on in vivo studies of DLCs which have a structural relationship to dioxins, bind to the AhR, and elicit AhR-mediated biochemical and toxic responses, allowing for risk assessment of DLCs as a complex mixture (Van den Berg et al., 2006).
Dioxins are primarily a health concern as human carcinogens (Baan et al., 2009), however, recent attention is on their endocrine disrupting properties, particularly at low exposures. Experimental studies suggest that, as a down-stream function of AhR activation, dioxins are endocrine disrupting chemicals (EDCs), including effects on thyroid function, insulin and growth (Kogevinas, 2001). The direction of the effect on growth is, however, not entirely clear. For example, in vitro, adipocyte differentiation was inhibited by TCDD (⩾ 0.1 nM) (Bastos Sales et al., 2013). In female adult mice fed a high fat diet, high doses but not low doses of TCDD induced obesity (Zhu et al., 2008). Few epidemiological studies have investigated perinatal exposure to dioxins and indicators of obesity, and the evidence is also inconclusive (Delvaux et al., 2014, Nishijo et al., 2012, Patandin et al., 1998, Su et al., 2010, Verhulst et al., 2009, Wohlfahrt-Veje et al., 2014). Previous studies were in smaller samples (Delvaux et al., 2014, Su et al., 2010, Verhulst et al., 2009), or only studied body mass index (BMI) and other fat measures during infancy (Nishijo et al., 2012, Patandin et al., 1998, Verhulst et al., 2009, Wohlfahrt-Veje et al., 2014) and not later in childhood.
We investigated the association between perinatal exposure to dioxins and infant growth and BMI in later childhood in three European birth cohorts.
Section snippets
Description of cohorts
Within the framework of the EU project OBELIX (Legler et al., 2011) a collaboration was established between 3 European birth cohorts: the Norwegian HUMIS study (Eggesbø et al., 2009, Eggesbø et al., 2011), the Flemish FLEHS I study (Koppen et al., 2009) and the Slovak PCB cohort (Hertz-Picciotto et al., 2003). Table 1 contains cohorts' descriptions and references. The mother-child pairs were recruited in the period from 2002 until 2004 (PCB cohort N = 1137, FLEHS I, N = 1196) and until 2009 (HUMIS,
Results
Table 3 describes the study populations in which dioxin exposure was assessed. Mothers were mostly non-smokers during pregnancy, Caucasian (except for a fifth of the PCB cohort who were Roma) and with a median pre-pregnancy BMI of 26–27. They were oldest in FLEHS I and youngest in PCB cohort. FLEHS I mothers breastfed their babies for the shortest time (median 3.0 months), while median duration of total breastfeeding in HUMIS mothers was 11.0 months. Unlike the other two cohorts with medium
Discussion
In our pooled analysis of 3 European birth cohorts, perinatal dioxin exposure had a borderline significant association with greater infant growth and a significantly increased BMI in 7 year old girls but not boys. The elevated BMI was due to weight and not height, and corresponded to an increased risk of overweight.
The increased growth between birth and 24 months was borderline significant in both the total population and in girls, although there was no significant interaction by sex. There were
Conclusion
In the first study on perinatal exposure to dioxins and BMI in school aged girls and boys, exposure appeared associated with increased infant growth in girls and boys and was significantly associated with BMI at 7 years in girls, corresponding to increased risk for overweight. These relations need to be investigated in larger sample sizes to see if the sex-specific effects of dioxins on BMI still hold.
Acknowledgements
Funding was received from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreements OBELIX n° 227391 and Early Nutrition n° 289346 and by funds from the Norwegian Research Council's MILPAAHEL programme, project No. 213148. Additional information on funding for the individual cohorts can be found in the Supplemental Material. The authors would like to thank all participants for their generous collaboration. We thank Martin van Velzen and Jacco Koekkoek from IVM
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Current address: Brunel University London, Institute of Environment, Health and Societies, Uxbridge, UK.